1. Field
The present invention relates to a strain of genus streptococcus by which high molecular weight hyaluronic acid can be produced with a high yield, and a method of producing hyaluronic acid using the same. More particularly, the present invention relates to a Streptococcus dysgalactiae ID9103 strain having an accession number of KCTC11818BP, and a method of producing hyaluronic acid comprising culturing the strain.
2. Discussion of the Background
Hyaluronic acid ((HA), Hyaluronan, (C14H20NNaO11)n (n>1000)) is a polymer existing throughout living organisms, and is a polysaccharide, called glycosaminoglycan. It has a structure which is composed of alternating D-glucuronic acid and N-acetylglucosamine, linked together via alternating β-1,3 and β-1,4 glycosidic bonds. It is a water-soluble material and its usable molecular weight has a wide range of 1,000 to 10,000,000 Da (daltons). Also, it has a structure of a straight chain.
The hyaluronic acid with salt structure shows a high efficacy and a high effect, and shows a strong lubricative effect in a physical friction state due to its high moisturizing effect. Also, it has preferable advantages in various effects and properties such as protection against bacterial invasion, etc. Thus, the development using the hyaluronic acid has been recently conducted in the field of medical treatment. These advantages can be applied to medical supplements, bio materials, and foods as well as play a role in medical supplies or cosmetics. Further, novel fields based on hyaluronic acid have been continuously developed.
In order to develop hyaluronic acid, a biological tissue extraction method or a microorganism culturing method is used. however, since a chicken comb extraction method causes many disadvantages such as virus invasion, impurities, and inflammatory reactions, a microorganism culturing production method has been recently mainly used in which a molecular weight and productivity can be controlled, and a high quality of raw materials can be obtained. Especially, in a recent tendency, according to the range of a molecular weight of hyaluronic acid adjusted and produced by microorganism culturing, use of hyaluronic acid is determined. Ultra-low molecular weight hyaluronic acid of 100,000 Da or less is mainly used for foods or cosmetics, and low molecular weight hyaluronic acid with an average molecular weight of 1,000,000 Da is utilized for developing an eye-drops raw material or its derivative, and hyaluronic acid with an average molecular weight of 3,000,000 to 4,000,000 Da is highly valuable when utilized as a knee joint injection raw material.
Of course, there is much room for hyaluronic acid with a range of higher molecular weights to be very variously utilized. It is expected that its utilization as a knee joint therapeutic agent but also as an ophthalmic surgery adjuvant can be highly increased. Moreover, since a role of ultra-high molecular weight hyaluronic acid is needed in many areas within a body, the ultra-high molecular weight hyaluronic acid may sufficiently substitute for a conventional hyaluronic acid linking material obtained by increasing the molecular weight, the viscosity or the elasticity of relatively low molecular weight hyaluronic acid.
It can be found that most of main patents applied in Korea are limited to invention of high molecular weight hyaluronic acid. Korean Registered Patent No. 10-0250573 (LG) discloses production of hyaluronic acid of 3,500,000 Da, and Korean Registered Patent 10-0472007 (Vacctech, Kolon) discloses a technology of producing hyaluronic acid with an average molecular weight of 5,500,000 Da. Most of foreign countries (U.S. Pat. No. 4,784,990, JP2058502, and EP144019) have technologies of producing hyaluronic acid of 4,000,000 Da or less. Especially, in a case of the technology of U.S. Pat. No. 6,090,596, hyaluronic acid with a high molecular weight can be produced, but it is difficult to industrially use this technology in actuality due to its very low productivity and its production method, and also its economical efficiency is not secured.
It is known that generally widely developed hyaluronic acid with a high molecular weight of 3,000,000˜4,000,000 Da is very insufficient in view of efficacy/effect to be applied to in a medical field requiring high viscosity/elasticity. In order to solve such a disadvantage, it is required to invent a technology for economically efficiently producing hyaluronic acid with an ultra-high molecular weight of 6,000,000 Da or more. Further in order to properly develop ultra-high molecular weight hyaluronic acid as a highly value-added industrial drug, the technology has to be developed as a technology with competitiveness and economical efficiency through the most creative method.
Accordingly, in order to overcome the disadvantage, it is required to develop a method of producing high molecular weight hyaluronic acid with high productivity through creative and economically efficient composition of a microorganism culture medium, and application of a mass production technology.